Ankhd1, or ankyrin repeat and single KH domain-containing protein 1, is a large scaffolding protein. It has two stretches of ankyrin repeat domains for protein-protein interactions and a KH domain for RNA or single-stranded DNA binding. ANKHD1 is involved in crucial signalling pathways such as receptor tyrosine kinase, JAK/STAT, mechanosensitive Hippo (YAP/TAZ), and p21, and is important in regulating cellular processes [1,3].

In cancer research, silencing of ANKHD1 in various cancer cell lines has shown significant effects. In triple-negative breast cancer (TNBC) cells, ANKHD1 silencing reduced viability, clonogenicity, and migration [2]. In hepatocellular carcinoma, knocking down ANKHD1 attenuated the pro-migratory and pro-invasive effects of SMYD3 [4]. In multiple myeloma cells, ANKHD1 silencing led to decreased cell proliferation, accumulation at the S phase, down-regulation of core histones, and modulation of genes related to DNA repair [5]. In non-small-cell lung cancer (NSCLC), depletion of ANKHD1 abolished its promoting effects on cell proliferation and invasion [6]. In multiple myeloma, ANKHD1 silencing decreased in vitro clonogenicity and in vivo tumourigenicity [7].

In conclusion, Ankhd1 is essential in regulating histone synthesis, DNA repair, and cell cycle progression. Studies using gene-silencing (a form of functional loss-of-function similar to KO in cell lines) have revealed its significant role in cancer, promoting tumour growth, metastasis, and contributing to a poor prognosis in various cancer types. These findings suggest Ankhd1 could be a potential target for cancer treatment.

References:

1. Mullenger, Jordan L, Zeidler, Martin P, Fragiadaki, Maria. 2023. Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer. In International journal of molecular sciences, 24, . doi:10.3390/ijms241612834. https://pubmed.ncbi.nlm.nih.gov/37629022/

2. de Almeida, Bruna O, de Almeida, Larissa C, Costa-Lotufo, Leticia V, Machado-Neto, João A. 2022. ANKHD1 contributes to the malignant phenotype of triple-negative breast cancer cells. In Cell biology international, 46, 1433-1446. doi:10.1002/cbin.11844. https://pubmed.ncbi.nlm.nih.gov/35842770/

3. Almeida, Bruna Oliveira de, Machado-Neto, João Agostinho. . Emerging functions for ANKHD1 in cancer-related signaling pathways and cellular processes. In BMB reports, 53, 413-418. doi:. https://pubmed.ncbi.nlm.nih.gov/32635985/

4. Zhou, Zhenyu, Jiang, Hai, Tu, Kangsheng, Xiao, Zhiyu, He, Chuanchao. 2019. ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma. In Journal of experimental & clinical cancer research : CR, 38, 18. doi:10.1186/s13046-018-1011-0. https://pubmed.ncbi.nlm.nih.gov/30646949/

5. Dhyani, Anamika, Favaro, Patricia, Olalla Saad, Sara T. 2020. ANKHD1 is an S phase protein required for histone synthesis and DNA repair in multiple myeloma cells. In Blood cells, molecules & diseases, 84, 102460. doi:10.1016/j.bcmd.2020.102460. https://pubmed.ncbi.nlm.nih.gov/32562952/

6. Liu, Xiao-Fang, Han, Qiang, Rong, Xue-Zhu, Yu, Juan-Han, Lin, Xu-Yong. 2020. ANKHD1 promotes proliferation and invasion of non‑small‑cell lung cancer cells via regulating YAP oncoprotein expression and inactivating the Hippo pathway. In International journal of oncology, 56, 1175-1185. doi:10.3892/ijo.2020.4994. https://pubmed.ncbi.nlm.nih.gov/32319569/

7. Dhyani, Anamika, Machado-Neto, João A, Favaro, Patricia, Saad, Sara T Olalla. 2014. ANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growth. In European journal of cancer (Oxford, England : 1990), 51, 252-9. doi:10.1016/j.ejca.2014.11.012. https://pubmed.ncbi.nlm.nih.gov/25483783/